• Korean Journal of Microbiology
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• v.42 no.4
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• pp.319-325
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• 2006

[ $\beta$ ]-Glucans (AG) were prepared from Agaricus blazei cultured in the medium fortified with the roots of Pueraria spp. by repeated extraction with hot water, gel filtration chromatography and DEAE ion exchange chromatography. Oligosaccharides (AO) were derived from the hydrolysis of AG by an endo-$\beta$-(1$\rightarrow$6)-glucanase from Bacillus megaterium. The anti-HT-29 human colon cancer activity of AG or AO was investigated using MTT assay, apoptosis assay, cell cycle analysis, and cDNA microairay. AG and AO both inhibited proliferation and growth of HT-29 cells, and stimulated apoptosis of the cells in a dose-dependent manner. In cell cycle analysis, treating HT-29 cells with AG or AO resulted in the increase of cells in the G0 (sub-G1) and G1 phase. Especially, AO was more effective in inducing G0/G1 cell cycle arrest than AG. To screen the genes involved in the increase of apoptosis, the gene expression profile of the HT-29 cells treated with AO was examined by cDNA microarray. While several genes involved in cell cycle progression (CCND2 and CDK2) were down-regulated, many genes involved in apoptosis (TNFSF9, TNFRSF9, FADD, CASP8, BAD, CRADD, CASP9 etc), cell cycle inhibitor (CDKN2A), immune response (IL6, IL18, IL6R etc), and tumor suppressor (CEACAM1, TP53BP2, IRF1, and PHB) were up-regulated. These results suggest that AO could inhibit the proliferation and growth of HT-29 cells by G0/G1 cell cycle arrest and induction of apoptosis.

• Nuclear Medicine and Molecular Imaging
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• v.41 no.3
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• pp.209-217
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• 2007

Purpose: Multidrug resistance (MDR) of the cancer cells related to mdr1 gene expression can be effectively treated by selective short hairpin RNA for mdr1 gene (shMDR). Sodium/iodide symporter (NIS) gene is well known to have both reporter and therapeutic gene characteristics. We have co-transfected both shMDR and NIS gene into colon cancer cells (HCT15 cell) expressing MDR and Tc-99m sestamibi and I-125 uptake were measured. In addition, cytotoxic effects of doxorubicin and I-131 therapy were also assessed after transfection. Material and Methods: At first, shMDR was transfected with liposome reagent into human embryonic kidney cells (HEK293) and HCT cells. shMDR transfection was confirmed by RT-PCR and western blot analysis. Adenovirus expressing NIS (Ad-NIS) gene and shMDR (Ad-shMDR) were co-transfected with Ad-NIS into HCT15 cells. Forty-eight hours after infection, inhibition of P-gycoprotein (Pgp) function by shMDR was analyzed by a change of Tc-99m sestamibi uptake and doxorubicin cytotoxicity, and functional activity of induced NIS gene expression was assessed with I-125 uptake assay. Results: In HEK293 cells transfected with shMDR, mdr1 mRNA and Pgp protein expressions were down regulated. HCT15 cells infected with 20 MOI of Ad-NIS was higher NIS protein expression than control cells. After transfection of 300 MOI of Ad-shMDR either with or without 10 MOI of Ad-NIS, uptake of Tc-99m sestamibi increased up to 1.5-fold than control cells. HCT15 cells infected with 10 MOI of Ad-NIS showed approximately 25-fold higher I-125 uptake than control cells. Cotransfection of Ad-shMDR and Ad-NIS resulted in enhanced cytotoxic by doxorubicin in HCT15 cells. I-131 treatment on HCT15 cells infected with 20 MOI of Ad-NIS revealed increased cytotoxic effect. Conclusion: Suppression of mdr1 gene expression, retention of Tc-99m sestamibi, enhanced doxorubicin cytotoxicity and increases in I-125 uptake were achieved in MDR expressing cancer cell by co-transfection of shMDR and NIS gene. Dual therapy with doxorubicin and radioiodine after cotransfection shMDR and NIS gene can be used to overcome MDR.

• Korean Journal of Food Science and Technology
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• v.30 no.6
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• pp.1470-1475
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• 1998

Two kinds of Korean rice-wine (Yakju) with different process and ingredients, and Japanese rice-wine (Sake) were chosen for this study, and throughly dried and solubilized in water or cell culture medium. In vitro cytotoxicity assays of the solubilized wine solids exhibited that maximum dilution factors for inhibition of B 16BL6 mouse melanoma cell growth were 16X for herbal medicine-added rice-wine (Korean rice-wine I) and typical Korean rice-wine (Korean rice-wine II), and 8X for Japanese rice-wine. Their cytotoxic effects on HRT18 human colon adenocarcinoma cells were even lower than those on B16BL6 cells. The morphology of the tumor cells were changed by addition of the solubilized wine solids. Inhibitory effect of the rice-wine on in vivo tumor growth and metastasis were monitored after implantation of B16BL6 cells into C57BL/6 mice with daily feeding the solubilized wine solids. Compared to non-fed control groups, B16BL6 tumor growth and metastasis to lung were clearly inhibited by feeding the wine solids, in order of Korean rice-wine I > Korean rice-wine II > Japanese rice-wine. The data of in vitro cytotoxicity and the cell shape changes indicate that the inhibitory effect of tumor progression may be attributed to tumor cell differentiation or immune stimulation induced by certain components in the rice-wine, rather than direct cytotoxicity of the components.

• Journal of Life Science
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• v.32 no.3
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• pp.263-269
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• 2022

Cancer cachexia-anorexia is a multi-organ metabolic syndrome characterized by anorexia and weight loss. Generally, such symptoms are a serious problem in cancer patients, adversely affecting chemotherapy success and survival rate. Cachexia has been reported to accompany up to 80% of gastrointestinal cancers, such as pancreatic, lung, and colon cancer, though it is relatively rare in lymphoma or breast cancer patients. It is also known that cancer-induced anorexia occurs independently of chemotherapy, although decreased appetite due to chemotherapy is well reported. In terms of pathoflammatory cytokines that are excessively increased by tumor tissues. Since the mechanism of cancer cachexia is not yet fully understood, there are currently no therapeutic agents or diagnostic markers to treat it. A recently published study identified a substance secreted from cancer cells that induces cancer anorexia, and the molecular mechanism causing the eating disorder was discovered. An increase in the expression of this substance has been shown to be statistically correlated with the symptoms of cachexia in cancer patients, and it is therefore expected to be applicable in the diagnosis and development of therapeutic agents for cancer cachexia. This review article aims to provide an overview of the key molecular mechanisms of the anorexia and tissue wasting caused by cancer cachexia.

• The Korean Journal of Food And Nutrition
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• v.25 no.4
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• pp.941-950
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• 2012

In order to develop new physiologically active polysaccharides from persimmon leaves, two different crude polysaccharides were prepared using hot water (PLW-0) and pectinase digestion (PLE-0) and their immuno-stimulating activities were estimated. PLW-0 and PLE-0 showed similar sugar compositions with 15 different sugars, including rarely observed sugars in general polysaccharides such as 2-O-methyl-fucose, 2-O-methyl-xylose, apiose, aceric acid, 3-deoxy-D-manno-2-octulosonic acid, and 3-deoxy-D-lyxo-2-heptulosaric acid, but the uronic acid content of PLE-0 was lower than that of PLW-0 caused by pectinase treatment. Both PLW-0 and PLE-0 showed potent anti-complementary activity in a dose-dependent manner which was similar to a known immuno-stimulating polysaccharide, PSK, from Coriolus versicolor. The activity of PLE-0 at a low concentration ($100{\mu}g/m{\ell}$) was higher than that of PLW-0. In an in vitro cytotoxicity analysis, PLW-0 and PLE-0 (up to $1,000{\mu}g/m{\ell}$) did not affect the growth of peritoneal macrophages and Colon 26-M3.1 carcinoma cells. In contrast, they enhanced lymphocyte proliferation activity. Peritoneal macrophages stimulated with PLW-0 and PLE-0 produced various cytokines, such as IL-6 and IL-12. However, PLE-0 was more effective on the cytokine production. Intravenous administration of PLW-0 and PLE-0 significantly augmented natural killer (NK) cell cytotoxicity against Yac-1 tumor cells 3 days after the treatment of polysaccharide fractions. But NK cells obtained from the PLE-treated group showed higher tumoricidal activity even at a low dose of $40{\mu}g$/mouse. In experimental lung metastasis of Colon 26-M3.1 carcinoma cells, prophylactic administration of PLW-0 and PLE-0 significantly inhibited lung metastasis in a dose-dependent manner and PLE-0 was more effective on the inhibition of cancer metasasis. The results lead us to conclude that the pectinase-treated process is indispensable to preparing polysaccharides with higher immune-stimulating activity from persimmon leaves.

• Nutrition Research and Practice
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• v.4 no.5
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• pp.351-355
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• 2010

Our previous proteomic study demonstrated that oxidative stress and antioxidant delphinidin regulated the cellular level of $p27^{kip1}$ (referred to as p27) as well as some heat shock proteins in human colon cancer HT 29 cells. Current study was conducted to validate and confirm the regulation of these proteins using both in vitro and in vivo systems. The level of p27 was decreased by hydrogen peroxide in a dose-dependent manner in human colon carcinoma HCT 116 (p53-positive) cells while it was increased upon exposure to hydrogen peroxide in HT 29 (p53-negative) cells. However, high concentration of hydrogen peroxide (100 ${\mu}M)$ downregulated p27 in both cell lines, but delphindin, one of antioxidative anthocyanins, enhanced the level of p27 suppressed by 100 ${\mu}M$ hydrogen peroxide. ICR mice were injected with varying concentrations of hydrogen peroxide, delphinidin and both. Western blot analysis for the mouse large intestinal tissue showed that the expression of p27 was upregulated by 25 mg/kg BW hydrogen peroxide. To investigate the association of p27 regulation with hypoxia-inducible factor 1-beta (HIF-$1{\beta}$), the level of p27 was analyzed in wild-type mouse hepatoma hepa1c1c7 and Aryl Hydrocarbon Nuclear Translocator (arnt, HIF-$1{\beta}$)-defective mutant BPRc1 cells in the absence and presence of hydrogen peroxide and delphinidin. While the level of p27 was responsive to hydrogen peroxide and delphinidin, it remained unchanged in BPRc1, suggesting that the regulation of p27 requires functional HIF-$1{\beta}$. We also found that hydrogen peroxide and delphinidin affected PI3K/Akt/mTOR signaling pathway which is one of upstream regulators of HIFs. In conclusion, hydrogen peroxide and antioxidant delphinidin seem to regulate intracellular level of p27 through regulating HIF-1 level which is, in turn, governed by its upstream regulators comprising of PI3K/Akt/mTOR signaling pathway. The results should also encourage further study for the potential of p27 as a biomarker for intracellular oxidative or antioxidant status.

• Microbiology and Biotechnology Letters
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• v.41 no.4
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• pp.425-432
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• 2013

Typha orientalis, also known as bulrush or cattail, is a perennial herbaceous plant found in freshwater wetlands and has been widely used in constructed wetlands for wastewater treatment. Recent data has revealed that SH21B, a mixture composed of seven herbs including T. orientalis, exhibited an anti-adipogenic activity by the inhibition of the expression of adipogenic regulators. However, the anti-cancer effect of T. orientalis and its molecular mechanisms remain unclear. In this study, we evaluated the anti-cancer effect and its mechanism in the methanol extract of T. orientalis (METO) on human colon carcinoma HT29 cells. It was found that METO treatment showed cytotoxic activity in a dose-dependent manner, and induced G2/M cell cycle arrest and apoptosis in HT29 cells. The induction of G2/M arrest by METO was associated with the up-regulation of phospho-Cdc2 (Tyr15), an inactive form of Cdc2 and the down-regulation of Cdc25c phosphatase. METO also induced tumor suppressor p53 and cyclin-dependent kinase inhibitor p21 (WAF1/CIP1) expression. In addition, METO-induced apoptosis was characterized by the proteolytic activation of caspase-3, degradation of poly ADP ribose polymerase (PARP), and up-regulation of death receptor FAS and pro-apoptotic Bax expression. Collectively, these results indicate that the cell cycle inhibition and apoptosis induction of METO in HT29 cells allows for the possibility of its use in anti-cancer therapies.

• Journal of Life Science
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• v.19 no.12
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• pp.1737-1742
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• 2009

It has been known that Linum usitatissimum and Perilla frutescens are dietary sources of possible chemopreventive compounds such as lignans and $\alpha$-linolenic acid. Here, we investigated and compared the inhibitory effects of methanol extracts from Linum usitatissimum and Perilla frutescens on mutagenicity using the Ames test, and growth of human cancer cells (AGS human gastric adenocarcinoma, HT-29 human colon cancer, Hep 3B hepatocellular carcinoma cells). In the Ames test system using Salmonella typhimurium TA100, aflatoxin $B_1$ ($AFB_1$)-induced mutagenicity was significantly inhibited by treatment with the methanol extract from either Linum usitatissimum or Perilla frutescens (p<0.05) in a dose dependent manner. As for N-methyl-N'-nitro-N-nitrosoguamidine (MNNG)-induced mutagenicity, the methanol extracts (5 mg/assay) from Linum usitatissimum and Perilla frutescens showed 63% and 78% inhibitory rates, respectively, indicating that Perilla frutescens possessed stronger antimutagenic activity than did Linum usitatissimum. Inhibitory effects of methanol extracts from Linum usitatissimum and Perilla frutescens on the growth of human cancer cells (AGS, HT-29 and Hep 3B) appeared to increase dose dependently, and the inhibition was more effective against AGS and HT-29 compared to Hep 3B cells. Our results suggested that the methanol extract from Perilla frutescens showed stronger antimutagenic activity than that from Linum usitatissimumas assayed by the Ames mutagenic test, whereas the methanol extract from Linum usitatissimum was more effective than its counterpart for growth inhibition of human cancer cells. It is concluded that intake of Linum usitatissimum and Perilla frutescens as sources of omega-3 fatty acids will be beneficial for preventing cancer.

• Applied Microscopy
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• v.38 no.1
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• pp.43-50
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• 2008

Uncooked powered diet (Saengshik) composed of grains, vegetables, mushrooms and fruits have various physiological functions including strong antioxidant and potent anticancer effects by many kinds of bioactive phytochemicals. The objective of present study was to identify the anticancer effects of vitamin C and saengshik on colon cancer induced by CT-26 cell line in BALB/c mice. As the result, the tumor volumes of vitamin C-mixed diet group (VC) showed no significant differences compared with control group (C) after subcutaneous injection of CT-26 cell lines. However saengshik group (S) showed a significant effect, inhibiting the growth of cancer by 56.2% ($4.8{\pm}9.0\;mm^3$), 48.1% ($80.8{\pm}60.0\;mm^3$), 43.2% ($135.2{\pm}117.2\;mm^3$), 55.5% ($233.6{\pm}248.2\;mm^3$), 69.2% ($304.6{\pm}442.5\;mm^3$) and 70.7% ($464.9{\pm}705.9\;mm^3$) respectively as compared with C group at an interval of 5 days after injection of the CT-26 cells into mice. Also the final tumor volume of S group exerted a significant differences as compared with one of C group (p<0.05). Especially in the case of S group (n=10), the tumors in 2 of 10 mice entirely disappeared at 25th day. Our results suggest that saengshik possess a strong inhibitory action against tumor growth induced by CT-26 colon cancer cell line in the mice. Further studies of saengshik are required to confirm the cancer prevention effect and possibility of adjuvant cancer therapy.

• Korean Journal of Food Science and Technology
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• v.35 no.1
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• pp.132-137
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• 2003

Antioxidant and anti-inflammatory potentials of various grape extracts were evaluated. Extracts from Kyho seed, Kyho stem, and Campbell seed showed potent 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activities compared to resveratrol $(IC_{50}=16.9,\;21.5,\;21.9,\;34.6\;{\mu}g/mL,\;respectively)$, among which, antioxidant effect of Kyho seed extract were similar to that of vitamin C $(IC_{50}=12.2\;{\mu}g/mL)$. These extracts also exhibited inhibitory activities on lipopolysaccharide (LPS)-induced prostaglandin $E_2$ production and nitrite formation in mouse macrophage RAW 264.7 cells at $50\;{\mu}g/mL$. Kyho stem and seed extracts showed growth inhibitory activities in human lung and colon cancer cells. These results suggest the potential roles of grape extracts as antioxidants and anti-inflammatory agents.